Aims: This project previously explored environmental risk factors for leukemia. Current efforts focus on the influence of family cancer history as an independent predictor of risk and as a factor that enhances susceptibility in combination with other exposures. Few studies have evaluated the possible risk for adult leukemia associated with a family cancer history. Evidence for a link between family history and disease risk can provide the impetus for further studies of specific genes and modes of inheritance. In addition, family history of cancer is a composite variable representing shared genes as well as exposures. Family history may identify individuals with increased susceptibility due to increased likelihood of having one or more of several gene polymorphisms that are involved in cancer etiology. Such persons may be more likely, for example, to have known or unknown defects in DNA repair or to have polymorphisms in genes that affect metabolism of carcinogens. Procedures and techniques: Cases and controls provided information on cancer incidence and mortality in enumerated first and second degree relatives and on their own exposure to known and suspected risk factors for leukemia. Relatives reported to have died since the advent of the National Death Index (NDI) were linked with that database in an attempt to validate cause of death. For those reported to have died prior to the NDI, death certificates were requested from individual states. Analyses has focused on history of any cancer in any first degree relative, history of specific cancers in any first degree relative, and history of any or specific cancers in specific first degree relatives (e.g. in siblings) and on the relationship of family cancer history with risk for specific leukemia subtypes. Accomplishments: Death information was obtained from the National Death Index; approximately half of persons known to have died since the advent of the NDI could be matched. The low match rate was due to the lack of information on social security number and for some, the absence of complete or accurate birth dates. Death certificates were sought from individual states for those who died prior to the NDI and for those who died later but did not match or were uncertain matches. To date, for states that have been completed, death certificates have been retrieved for almost 70%. Analysis of self-reported data suggests that family history of cancer may increase risk for leukemia. Results differed for persons who reported data directly and those who required the help of a proxy-respondent. Reasons for this discrepancy are being explored. History of breast cancer in a sibling was strongly linked to leukemia risk. This observation is consistent with the hypothesis that possibility that persons with polymorphisms in genes that affect DNA repair may be at increased risk for leukemia and other cancers. Furthermore, there is preliminary evidence that persons with both a family history of breast cancer and smoking are at greater risk for leukemia than those with either one of these risk factors.